Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Clinical Effects of AMG 557 in Adults With Psoriasis

Inclusion Criteria: * Subjects must sign an Institutional Review Board (IRB)-approved informed consent form (ICF) before any study specific procedures. * Diagnosis of moderate to severe plaque PsO for at least 6 months prior to screening as defined by: * A minimum PASI score of ≥ 10 obtained at screening; * Psoriasis involving ≥ 10% of the Body Surface Area (BSA) at screening. * Received at least 1 previous phototherapy or systemic PsO therapy (but not within the 30 days before study drug administration), or has been a candidate to receive phototherapy or systemic PsO therapy in the opinion of the PI. * Stable treatment without topical or systemic steroids, topical or systemic retinoids, vitamin D analogues (Dovenex), Psoralen Ultraviolet A (PUVA) therapy, Ultraviolet A (UVA) therapy or Ultraviolet B (UVB) therapy, methotrexate, or cyclosporine for at least 60 days prior to IP administration. Stable treatment of PsO involving scalp, axillae, or groin with topical corticosteroids of moderate strength will be allowed. * Agrees to wear clothing that protects from sun exposure for the duration of the study. * Agrees to use sunscreen (SPF of at least 30) on sun-exposed skin for the duration of the study. * Male or female subjects between 18 and 55 years of age, inclusive at the time of screening. * Body mass index (BMI) between 18 and 35 kg/m2, inclusive, at screening, unless considered by the PI and the Amgen Medical Monitor to be at an appropriate value in the context of other measured safety parameters. * Able and willing to complete entire study (including skin biopsies) according to study schedule. * Additional criteria per protocol. Exclusion Criteria: * Diagnosis of guttate, pustular, or other non plaque forms of PsO. * Evidence of skin conditions other than PsO (eg, eczema) during the screening period that would interfere with evaluations of the effect of IP on PsO. * Previous receipt of any approved or investigational biologic agent for PsO or other medical conditions. * Received PUVA therapy, UVA therapy or UVB therapy ≤ 30 days prior to IP administration. * Treatment with any other systemic PsO therapy or oral or parenteral corticosteroids ≤ 30 days prior to IP administration. * Use of high potency topical steroids, topical vitamin A or D analog preparations, or anthralin ≤ 30 days prior to IP administration (Note: stable doses \> 30 days of low or moderate strength topical steroids are permitted only on the scalp, axillae, and groin according to the package insert). * Received topical cyclosporin or calcineurin inhibitors such as pimecrolimus (Elidel) and tacrolimus (Protopic) ≤ 30 days prior to IP administration. * Received IV or oral calcineurin inhibitors such as tacrolimus (Prograf) ≤ 30 days prior to IP administration. * Significant concurrent medical conditions at the time of screening or prior to randomization, including: * Uncontrolled hypertension (defined as screening systolic blood pressure measurement of greater than 140 mm Hg or a screening diastolic blood pressure of greater than 90 mm Hg) confirmed by 2 separate measurements during the screening visit; * Unstable angina pectoris; * Congestive heart failure; * Steroid or oxygen dependent chronic obstructive pulmonary disease; * Diagnosis of multiple sclerosis or any other demyelinating disease; * Open cutaneous ulcers; * Uncontrolled diabetes (HbA1c \> 7%). * History of myocardial infarction. * Subjects with two or more cardiovascular risk factors (defined as BMI \> 30, BP systolic \> 140 mm Hg, diagnosis of diabetes, history of cardiovascular event). * Evidence of significant renal insufficiency during the screening period, defined by a glomerular filtration rate \< 50 mL/min using the Cockcroft and Gault equation: 72 x Serum Creatinine (in mg/dL) / (140 - Age) x Body Weight (in kg) x \[0.85 if female\] * Evidence of any bacterial, viral, parasitic, or systemic fungal infections during the 30 days prior to study drug administration (eg, common cold, viral syndrome, flu like symptoms). * Evidence of a recent (within 6 months of randomization) infection requiring in patient hospitalization or intravenous antibiotics. * Positive test for HIV antibodies, hepatitis B surface antigen, or hepatitis C antibodies. * Underlying condition that predisposes the subject to infections (eg, history of splenectomy; history of immunodeficiency). * Evidence of past or active tuberculosis on chest x-ray performed during screening (or documented evidence on a chest x-ray performed within 6 months prior to planned dosing); known tuberculosis antecedents; known exposure (without adequate treatment) to a person with active tuberculosis; or positive protein purified derivative (PPD) Mantoux skin or serum quantiferon test at screening (without documented history of treatment). A positive result is defined as either induration greater than or equal to 5 mm 48-72 hours after administration (Mantoux) or a positive serum quantiferon test result. * History of malignancy. * Evidence of liver disease (eg, serum ALT and AST \> 1.5 x the upper limit of normal) during screening period. * Donated blood (including blood products) or experienced loss of blood ≥ 500 mL within 2 months of screening. * Additional criteria per protocol.